A focused sulfated glycoconjugate Ugi library for probing heparan sulfate-binding angiogenic growth factors |
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Authors: | Ligong Liu Caiping Li Siska Cochran Daniel Feder Luke W Guddat Vito Ferro |
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Affiliation: | Progen Pharmaceuticals Limited, Brisbane, Qld 4076, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld 4072, Australia. Electronic address: l.liu@imb.uq.edu.au. |
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Abstract: | A library of small molecule heparan sulfate (HS) mimetics was synthesized by employing the Ugi four-component condensation of d-mannopyranoside-derived isocyanides with formaldehyde as the carbonyl component and a selection of carboxylic acids and amines, followed by sulfonation. The library was used to probe the subtle differences surrounding the ionic binding sites of three HS-binding angiogenic growth factors (FGF-1, FGF-2 and VEGF). Each compound features 3 or 4 sulfo groups which serve to anchor the ligand to the HS-binding site of the protein, with a diverse array of functionality in place extending from C-1 or C-6 to probe for adjacent favorable binding interactions. Selectivity of binding to these proteins was clearly observed and supported by molecular docking calculations. |
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